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GSE39621
Mus musculus
51 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional neurological, lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1-/- mice (Npc1nih)relative to Npc1+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates for the neurological disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gauchers disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1-/- as well as Balb/c Npc1nmf164 mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry.
Publication Title
Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Natural killer (NK) cells induce apoptosis in infected and transformed cells and produce immunoregulatory cytokines. At this, NK cells operate in inflammatory and tumor environments low in oxygen (hypoxic) and with immunosuppressive properties. In vitro studies of NK cells are, however, commonly performed in ambient air (normoxia).
Publication Title
Short Term Hypoxia Synergizes with Interleukin 15 Priming in Driving Glycolytic Gene Transcription and Supports Human Natural Killer Cell Activities.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Bos taurus
- 36 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Publication Title
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 321 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the hosts inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.94, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.
Publication Title
Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Recent observations about how cells sense amino acids have argued for preeminent roles of mTOR and the stress kinase GCN2 in allowing cells to estimate their amino acid needs. Here we used models of programmed immune microenvironments where helper T cells have to sense how much amino acids are available to engage in antigen-fueled proliferation. Contrary to current models, T cells activate mTOR in the competency phase of the cell cycle regardless of amino acid amounts, GCN2 or surface TCR. Instead, we found T cells use an amino acid sensing system to target IL-2-induced STAT5 phosphorylation at the restriction point of cell cycle commitment. mTOR activity is subsequently reduced and specifically connected to SREBP activation. T cells can be pushed into cycle by increasing IL-2 even when no amino acids are available. Collectively, our studies reveal helper T cells use sequential and distinct pathways to measure local amino acid concentrations.
Publication Title
Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Integrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
Publication Title
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
Illumina Genome Analyzer IIx
Description
A total of 332 genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in ten human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in three human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Long term exposure to incretin hormones is known to have salutory effects on beta cell function and viability. While short-term cAMP induction is known to have a signature CREB-CRTC target gene response, the long-term effects of cAMP on beta cell gene expression are less well understood.
Publication Title
mTOR links incretin signaling to HIF induction in pancreatic beta cells.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HiSeq 2500
Description
We report RNA-sequencing data of 80 tumor-educated blood platelet (TEP) samples isolated from 39 patients with lower-grade glioma (LGG) and 41 healthy donors (HD). This dataset can be employed as input for the thromboSeq source code (available via GitHub: https://github.com/MyronBest/) to reproduce the thromboSeq drylab pipeline. Overall design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the humane reference genome using STAR, and intron-spanning reads were summarized using HTSeq.
Publication Title
RNA sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples